The objective of this project is to elucidate the mechanisms that govern the induction and regulation of autoimmunity, using experimental allergic encephalomyelitis (EAE) as a model. Specifically, we will continue studies of EAE induced without adjuvant by culturing spleen or peritoneal cells from nonimmune Lewis rats with myelin basic protein. Although these cultured cells do not induce EAE following transfer to syngeneic primary recipients, when spleen cells from these recipients are cultured with basis protein they transfer EAE to secondary recipients. The production of EAE without adjuvant using antigen-cultured cells from naive donors may provide a clearer understanding of the mechanisms of autoimmune disease induction. We will determine whether natural suppressor cells in the primary recipients of antigen-cultured cells prevent these animals from developing EAE. We will study the triggering events that lead to autoimmune disease without the drawbacks previously associated with the use of adjuvants. We will also study the cellular interactions involved in the induction of EAE, characterize the relevant cell populations and cell-derived factors, and begin to elucidate the effector mechanisms of EAE. Since EAE serves as a prototype for human demyelinating diseases such as multiple sclerosis, this investigation should provide insight into the etiology of these disorders.